1B Foundations 2 - Teratogenesis Flashcards
What embryonic structure (derived from the hypoblast) serves as a secondary energy source?
Endodermal yolk sac
What embryonic structure serves as a reservoir of nonspecialized (undifferentiated) stem cells?
Endodermal yolk sac
What are the three germ layers that derive from the epiblast?
Ectoderm
Mesoderm
Endoderm
Fetal development weeks 3-8. Embryonic period.
Organogenesis
Neural tube formed by neuroectoderm and closes by week four
Extremely susceptible to teratogens
Fetal development within week 1
hCG secretion begins after implantation of blastocyst
Fetal development within week 2
Bilaminar disc (epiblast, hypoblast) 2 weeks = 2 layers
Fetal development week 4
Heart begins to beat. 4 chambers.
Upper and lower limb buds begin to form
4 week = 4 limbs
Fetal development within week 3
Trilaminar disc
3 weeks = 3 layers
Gastrulation
Primitive streak, notochord, mesoderm and its organisation, and neural plate begin to form
Fetal development day 0
Fertilization by sperm forming zygote, initiating embryogenesis
Fetal development week 8 (Start of fetal period (movement begins))
Fetal movement, fetus looks like a baby
Eight rhymes with gait
Fetal development week 10
Genitalia have male/female characteristics.
TEN rhymes with PENis
ACE inhibitors causes which teratogenic malformations?
Renal
Aminoglycosides causes which teratogenic malformations?
CN VIII toxicity (Ototoxicity)
“A MEAN GUY hit the baby in the ear”
Fluoroquinolones causes which teratogenic malformations?
Cartilage damage (Animal studies)
Tetracylines causes which teratogenic malformations?
Discolored teeth
Cyclophosphamide causes which teratogenic malformations?
Ear/facial anomalies, limb hypoplasia, absence of digits
Methotrexate causes which teratogenic malformations?
Neural tube defects (interferes with folate metabolism), abortion (abortifacient)
Category X drug
Carbamazepine causes which teratogenic malformations?
Fetal hydantoin syndrome. Neural tube defects, craniofacial defects, fingernail hypoplasia, developmental delay, IUGR (Intrauterine Growth Restriction)
Valproic acid causes which teratogenic malformations?
Inhibition of maternal folate absorption –> neural tube defects
Phenytoin causes which teratogenic malformations?
Fetal hydantoin syndrome: microcephaly, dysmorphic craniofacial features, hypoplastic nails and distal phalanges, cardiac defects, IUGR, mental retardation
Lithium causes which teratogenic malformations?
Ebstein’s anomaly (atrialized right ventricle)
Statins causes which teratogenic malformations?
CNS and limb abnormalities
(Interferes with cholesterol metabolism)
Category X drug
Warfarin causes which teratogenic malformations?
Facial/limb/CNS anomalies, spontaneous abortion, bone deformities, fetal hemorrhage, opthalmological abnormalities.
“Not WARFARe on baby. HEPpy baby”
Category X drug
Isotretinoin causes which teratogenic malformations?
Spontaneous abortions
Category X drug
Diethylstilbestrol (DES) causes which teratogenic malformations?
Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies
Category X drug
Thalidomide causes which teratogenic malformations?
Limb defects (Phocomelia)("flipper" limbs) Category X drug
Non-medicinal-drug causes whith teratogenic potential?
Ionizing radiation Excessive vitamin A Maternal diabetes Iodine deficiency Cocaine, tobacco
Fetal Alcohol Syndrome features
Smooth philtrum Thin upper lip Small palpebral fissures Wide set eyes (Also cleft lip/palate)
Developmental delay
Intellectual disability
Nr one cause for intellectual disability in USA
Microcephaly
Holoprosencephaly
Synpolydactyly Definition?
Extra fused digits (i.e. between 3rd and 4th fingers)
Homeobox (HOX) Genes. What do they do?
Blueprint for skeletal morphology
Code for transcription regulators
Mutation in HOXD-13?
Synpolydactyly (between 3rd and 4th fingers)
What can alter HOX gene expression?
Retinoic acid
HOX mutations (in general)
Appendages in wrong locations
Where are Sonic hedgehog genes produced?
Base of limbs in zone of polarizing activity
What are Sonic hedgehog genes involved in?
Patterning along anterior-posterior axis.
Involved in CNS development.
Mutation in Sonic hedgehog genes causes?
Holoprosencephaly
Where is the Wnt-7 gene produced?
Apical ectoderm ridge
What is the Wnt-7 gene involved in?
Necessary for proper organization along dorsal-ventral axis. (So that feet and nose point in the same direction)
Where is the FGF gene produced?
Apical ectodermal ridge
What is the FGF gene involved in?
Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs.
Mutation in FGF gene causes?
Short limbs
Which antibiotics are potentially teratogenic?
Aminoglycosides
Tetracyclines
Fluoroquinolones
Pregnancy category X drugs?
Methotraxate Statins Warfarin Isotretinoin Diethylstilbestrol Thalidomide
Most common cause of neural tube defects?
Folate deficiency
Also: Most common vitamin deficiency in the US
Most common cause of congenital malformations in the US?
Alcohol use in pregnancy
Most common cause of congenital intellectual disability in theUS?
Fetal alcohol syndrome